Implantable device for delivering cardiac drug therapy

ABSTRACT

An implantable medical device in which an electrogram is recorded and analyzed in order to detect changes indicative of cardiac ischemia. Cardiac ischemia may be detected by recording an electrogram from a sensing channel of the device and comparing the recorded electrogram with a reference electrogram. If cardiac ischemia is detected, a cardiac drug such as a thrombolytic agent is delivered.

CROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] This application is related to U.S. application Ser. No.09/962,852, filed on Sep. 25, 2001, the specification of which is hereinincorporated by reference.

FIELD OF THE INVENTION

[0002] This invention pertains to implantable devices for detecting andtreating cardiac disorders.

BACKGROUND

[0003] A major cause of cardiac death is acute coronary occlusioncausing myocardial ischemia which results in a myocardial infarction orprecipitates a lethal arrhythmia. Most patients currently treated forventricular arrhythmias with an implantable cardioverter-defibrillator(ICD) have concurrent coronary artery disease, making them highlysusceptible to ischemic events that may result in death. Althoughpresently available ICDs can be beneficial during an acute ischemicepisode by terminating any resulting arrhythmias with electricalstimulation, they do nothing to directly treat the occlusion. Presentmedical treatments are successful in managing acute coronary occlusionby dissolving the thrombus with chemical agents and preventing itsreformation. Such treatments are generally performed only in anemergency-room setting, however, and in certain circumstances, onlyimmediate relief from the ischemia can save the patient's life.

SUMMARY OF THE INVENTION

[0004] The present invention relates to an implantable cardiac devicewith the capability of detecting ischemic events and delivering cardiacdrug therapy in response thereto. Such a device may be configured toalso operate as a cardiac pacemaker and/or ICD. In order to detectischemic events, the sensing channels of the device record anelectrogram that is analyzed to detect changes indicative of cardiacischemia. Upon detection of an ischemic event, the device is configuredto automatically deliver a cardiac drug such as a thrombolytic agent.The recorded and analyzed electrogram may cardiac drug such as athrombolytic agent. The recorded and analyzed electrogram may representeither intrinsic cardiac activity or an evoked response to a pace wherethe device is also configured to deliver cardiac pacing. In the lattercase, the electrogram is recorded from an evoked response sensingchannel that senses the depolarization of the myocardium brought aboutby the delivery of a pacing stimulus, where the evoked response sensingchannel may be the sensing/pacing channel used for delivering thestimulus or another sensing channel, such as one dedicated for thatpurpose.

[0005] In order to detect an ischemic change, the electrogram iscompared with a reference electrogram to ascertain if a morphologicalmarker of ischemia is present, such as increased current of injury. Thecomparison may involve, for example, cross-correlating the recorded andreference electrograms or comparing ST segment amplitudes, slopes, orintegrations with reference values. Any of these means also allows thedegree of ischemia to be quantified to determine if drug therapy iswarranted.

BRIEF DESCRIPTION OF THE DRAWINGS

[0006]FIG. 1A is a block diagram of an exemplary cardiac device withdrug delivery capability.

[0007]FIG. 1B is a block diagram of components for analyzing thefrequency spectrum of intervals between heartbeats.

[0008]FIG. 2 illustrates ischemic changes in a recorded electrogram.

[0009]FIG. 3 shows an exemplary drug delivery drug delivery apparatusutilizing an intravenous catheter.

[0010] FIGS. 4A-B show an exemplary drug delivery apparatus utilizingpatch electrodes.

DETAILED DESCRIPTION

[0011] As noted above, chemical agents are available today that cansuccessfully treat cardiac ischemia due to coronary occlusion bydissolving the thrombus or blood clot. Such agents include tissueplasminogen activators (tPA), streptokinase, and similar drugs. Agentsare also available that do not directly dissolve existing blood clotsbut act to prevent further clotting. These agents include low and highmolecular weight heparin and anti-platelet drugs such as aspirin andsimilar drugs. Other drugs may also be administered to treat the effectsof the ischemia such as anti-arrhythmic agents, beta-blockers, nitrates,and angiogenic agents. Because time is often of the essence in treatingcardiac ischemic episodes, it would be beneficial for an implantabledevice to have the capability of automatically delivering cardiac drugsthat would either resolve the situation or stabilize the patient enoughso that further medical treatment could be obtained. Administration ofcardiac drugs is not without risk, however, especially thrombolyticagents or drugs that otherwise inhibit hemostasis. Nevertheless, certainselected patients could benefit from automatic drug administration if acondition warranting such administration could be detected withsufficient specificity. The present invention relates to an implantablemedical device that is configurable to automatically deliver one or morecardiac drugs upon detection of cardiac ischemia. The methods fordetection of such ischemia detailed below also allow the detection to bequantified so that the extent of ischemia can be ascertained. The devicemay then be programmed by a clinician to deliver drugs only whenischemia of a specified degree is present.

[0012] 1. Exemplary Hardware Platform

[0013] Cardiac rhythm management devices such as pacemakers and ICDs aretypically implanted subcutaneously in a patient's chest and have leadsthreaded intravenously into the heart to connect the device toelectrodes used for sensing, pacing, or delivery of defibrillationshocks. A programmable electronic controller causes the pacing pulses tobe output in response to lapsed time intervals and sensed electricalactivity (i.e., intrinsic heart beats not as a result of a pacing pulse)or defibrillation shocks to be delivered when an arrhythmia is detected.The present invention may be incorporated into a pacemaker or ICD or adedicated device that is similarly implanted which is equipped withcardiac leads for sensing cardiac activity in order to detect ischemia.For illustrative purposes, however, a block diagram of an implantabledevice with dual-chamber pacing (i.e., the atria and ventricles) andcardioversion/defibrillation capability is shown in FIG. 1A. Thecontroller of the device is made up of a microprocessor 10 communicatingwith a memory 12, where the memory 12 may comprise a ROM (read-onlymemory) for program storage and a RAM (random-access memory) for datastorage. The controller could be implemented by other types of logiccircuitry (e.g., discrete components or programmable logic arrays) usinga state machine type of design, but a microprocessor-based system ispreferable. As used herein, the terms “circuitry” or “programmedcontroller” should be taken to encompass either custom circuitry (i.e.,dedicated hardware) or processor-executable instructions contained in amemory along with associated circuit elements.

[0014] The device has an atrial sensing/pacing channel comprising ringelectrode 43 a, tip electrode 43 b, sense amplifier 41, pulse generator42, and an atrial channel interface 40 which communicatesbidirectionally with a port of microprocessor 10. The device also has aventricular sensing/pacing channel that includes ring electrodes 33 a,tip electrodes 33 b, sense amplifier 31, pulse generator 32, and aventricular channel interface 30. For each channel, the electrodes areconnected to the pacemaker by a lead and used for both sensing andpacing. The channel interfaces may include analog-to-digital convertersfor digitizing sensing signal inputs from the sensing amplifiers,registers that can be written to for adjusting the gain and thresholdvalues of the sensing amplifiers, and registers for controlling theoutput of pacing pulses and/or changing the pacing pulse amplitude. AMOS switching network 70 controlled by the microprocessor is used toswitch the electrodes from the input of a sense amplifier to the outputof a pulse generator. A minute ventilation sensor 77 and anaccelerometer 78 are provided in order to sense the patient's minuteventilation and body activity, respectively. The device may use thesensed minute ventilation and/or the accelerometer signal to adjust therate at which the pacing pulses are delivered to the heart in theabsence of a faster intrinsic rhythm, sometimes called rate-adaptivepacing. A shock pulse generator 50 with shock leads 50 a and 50 b fordelivering cardioversion/defibrillation shocks is also interfaced to thecontroller.

[0015] The device also has an ischemia detection sensing channel thatcomprises an ischemia detection channel interface 20 and a senseamplifier 21 that has its differential inputs connected to a unipolarelectrode 23 and to the device housing or can 60 through the switchingnetwork 70. The ischemia detection channel may be used to record anelectrogram in order to detect ischemia as described below, where theelectrogram may represent either intrinsic cardiac activity or an evokedresponse to a pacing pulse. When configured to sense evoked responses,the channel can also be used to verify that a pacing pulse has achievedcapture of the heart and caused a contraction.

[0016] The microprocessor 10 controls the overall operation of thedevice in accordance with programmed instructions stored in memory. Thesensing circuitry of the device generates atrial and ventricular sensesignals when electrogram signals sensed by the electrodes exceed aspecified threshold. The controller then interprets sense signals fromthe sensing channels and controls the delivery of paces in accordancewith a programmed pacing mode. The sense signals from any of the sensingchannels of the device can also be digitized and recorded by thecontroller to constitute an electrogram that can be analyzed todetermine if ischemia is present, as well as either transmitted via atelemetry link 80 to an external programmer or stored for latertransmission. A drug delivery interface 330 enables the controller toactuate a drug delivery apparatus in order to deliver a cardiac drug tothe patient when an ischemic event is detected, where the drug may bedelivered in various ways as described below.

[0017] 2. Detection of Ischemia

[0018] In order to detect whether the patient is experiencing cardiacischemia, the controller is programmed to analyze the recordedelectrogram of an evoked response to a pace or of an intrinsiccontraction and look for morphological and temporal markers of a“current of injury.” When the blood supply to a region of the myocardiumis compromised, the supply of oxygen and other nutrients can becomeinadequate for enabling the metabolic processes of the cardiac musclecells to maintain their normal polarized state. An ischemic region ofthe heart therefore becomes abnormally depolarized during at least partof the cardiac cycle and causes a current to flow between the ischemicregion and the normally polarized regions of the heart, referred to as acurrent of injury. A current of injury may be produced by an infarctedregion that becomes continuously depolarized or by an ischemic regionthat remains abnormally depolarized during all or part of the cardiaccycle. A current of injury results in an abnormal change in morphologyand timing of the electrical potentials measured by either a surfaceelectrocardiogram or an intracardiac electrogram. In the normal heartthere is a period during the cardiac cycle, at the start of thecontraction phase, when the cells in the ventricle are essentiallyisopotential. Electrocardiographically this segment occurs between theend of the QRS complex and the T wave and is referred to as the STsegment. The spatio-temporal dispersion of repolarization starts therelaxation phase of the heart and results in the T-wave on theelectrocardiogram. In ischemic tissue, the individual cellularpotentials are blunted resulting in a spatial and temporal dispersion ofmembrane potential during periods when the normal heart is isopotential.This results in the current of injury which is reflected on theelectrocardiogram as a positive or negative shift, depending on thelocation of the ischemic or infarcted region. Traditionally, however, itis the ST segment that is regarded as shifted when an abnormal currentof injury is detected by an electrogram or electrocardiogram. A currentof injury produced by an ischemic region that does not last for theentire cardiac cycle may only shift part of the ST segment, resulting inan abnormal slope of the segment.

[0019] As aforesaid, an electrogram of an evoked response to a pace canbe recorded and used to detect cardiac ischemia in accordance with theinvention. An evoked response is the wave of depolarization that resultsfrom a pacing pulse and, since it evidences that the paced chamber hasresponded appropriately and contracted, it can also be used to verifythat the pace has achieved capture of the heart. Sensing channels in apacemaker that provide senses for controlling pacing are commonlyrendered refractory (i.e., insensitive) for a specified time periodimmediately following a pace in order to prevent the pacemaker frommistaking a pacing pulse or afterpotential for an intrinsic beat. Thisis done by the pacemaker controller ignoring sensed events during therefractory intervals, which are defined for both atrial and ventricularsensing channels and with respect to both atrial and ventricular pacingevents. Furthermore, a separate period that overlaps the early part of arefractory interval is also defined, called a blanking interval duringwhich the sense amplifiers are blocked from receiving input in order toprevent their saturation during a pacing pulse. If the same sensingchannel is used for both sensing intrinsic activity to control pacingand for sensing an evoked response, a period for sensing an evokedresponse should preferably be defined that supercedes any normalrefractory period of the sensing channel.

[0020] An ischemia detection-sensing channel for recording anelectrogram can be a sensing channel used for other purposes or can be asensing channel dedicated to sensing electrograms for ischemiadetection. In order to detect ischemic changes in an electrogram, it ispreferable to record the electrogram with a unipolar electrode that“sees” a larger volume of the myocardium as a wave of electricalactivity spreads than a bipolar electrode. In the embodiment illustratedin FIG. 1A, the atrial and ventricular sensing pacing channels utilizebipolar electrodes, and a dedicated ischemia detection sensing channelis provided with a unipolar electrode. Alternate embodiments may employunipolar electrodes in the atrial and/or sensing/pacing channels, inwhich case unipolar sensing of an electrogram for ischemia detection maybe performed with those channels instead of a dedicated channel.

[0021] A change in an electrogram indicative of ischemia is detected byrecording the electrogram and comparing it with a reference electrogram,which may either be a complete recorded electrogram or particularreference values representative of an electrogram. Because certainpatients may exhibit a current of injury in a reference electrogram as athe result of a subclinical ischemic condition (e.g., coronary arterydisease) or as the result of an inherited or aqurired disease(e.g.,Bruggada Syndrome), the controller is programmed to detect ischemia bylooking for an increased current of injury in the recorded electrogramas compared with the reference electrogram, where the latter may or maynot exhibit a current of injury. FIG. 2 shows examples of evokedresponse data for two cases labeled A and B, where A is the baselinereference and B is during an acute ischemic episode. A surfaceelectrocardiogram labeled ECG, a pacing timing diagram labeled PTD, andan electrogram labeled ER are illustrated for each case. The ST segmentof the electrogram for case B is seen to have a different amplitude andslope as compared with the amplitude and slope of the ST segment of theelectrogram for case A. One way to look for an increased current ofinjury in the recorded electrogram is to compare the ST segmentamplitude and/or slope with the amplitude and slope of a referenceelectrogram. Various digital signal processing techniques may beemployed for the analysis, such as using first and second derivatives toidentify the start and end of an ST segment. Other ways of looking for acurrent injury may involve, for example, cross-correlating the recordedand reference electrograms to ascertain their degree of similarity. Theelectrogram could be implicitly recorded in that case by passing theelectrogram signal through a matched filter that cross-correlates thesignal with a reference electrogram. The ST segment could also beintegrated, with the result of the integration compared with a referencevalue to determine if an increased current of injury is present.

[0022] If a change in a recorded electrogram indicative of ischemia isdetected, the device controller may be programmed to deliver athrombolytic agent or other cardiac drug by writing a command to thedrug delivery interface. Because of the risks attendant withadministering cardiac drugs in an uncontrolled setting, the drug shouldonly be delivered when the ischemia is severe enough to warrant it. Themethods for detecting ischemia in a recorded electrogram discussed aboveare advantageous in this regard because the degree of ischemia can bequantified as, for example, the extent of correlation between therecorded and reference electrograms, measured amplitude or slope of anST segment, or result of integrating the ST segment. The quantitativemeasure of ischemia necessary before the device delivers a drug dose canthen be adjusted by a clinician until the drug delivery criteria has thedesired specificity and sensitivity.

[0023] A detected ischemic change may also be logged as a clinicallysignificant event in the device's memory. The event log and/or therecorded electrogram exhibiting the ischemia may then be laterdownloaded to a clinician for analysis via an external programmer. Theclinician is then able to use this information in making subsequenttreatment decisions.

[0024] 3. Additional Criteria for Drug Delivery

[0025] As aforesaid, delivery of certain cardiac drugs can present risksto the patient. It is therefore desirable for the criteria used indetecting ischemic events that initiate therapy to be as specific aspossible in order to minimize the possibility of a false-positivedetection causing unwarranted drug delivery. As noted above, the presentinvention allows the degree of ischemia detected from an electrogram tobe quantified so that the ischemia detection criterion can be adjustedto the desired specificity and sensitivity. Another way of increasingthe specificity of event detection for drug delivery is to useadditional criteria based on other measurable physiological variableswhich correlate either with cardiac ischemia or with the need for drugdelivery during such events such as heart rate variability, minuteventilation, and activity level. Drug delivery can then be initiated ifischemic changes are detected in the electrogram and if one or more ofthe additional criteria are also met.

[0026] Cardiac ischemia causes metabolic stress that the body respondsto with increased activity of the sympathetic nervous system. Among theindicia of such increased sympathetic activity is the frequency spectrumof heart rate variability. Heart rate variability refers to thevariability of the time intervals between successive heart beats duringa sinus rhythm and is primarily due to the interaction between thesympathetic and parasympathetic arms of the autonomic nervous system.Spectral analysis of heart rate variability involves decomposing asignal representing successive beat-to-beat intervals into separatecomponents representing the amplitude of the signal at differentoscillation frequencies. It has been found that the amount of signalpower in a low frequency (LF) band ranging from 0.04 to 0.15 Hz isinfluenced by the levels of activity of both the sympathetic andparasympathetic nervous systems, while the amount of signal power in ahigh frequency band (HF) ranging from 0.15 to 0.40 Hz is primarily afunction of parasympathetic activity. The ratio of the signal powers,designated as the LF/HF ratio, is thus a good indicator of the state ofautonomic balance, with a high LF/HF ratio indicating increasedsympathetic activity. Additional specificity for initiating drugdelivery may thus be provided by monitoring the LF/HF ratio andinitiating drug therapy only if it exceeds a specified threshold value.The predetermined threshold value may be fixed or may be determined bythe device based upon previous measurements. For example, the LF/HFthreshold may be set to 50% of the maximum computed LF/HF ratio valueduring the previous day.

[0027] A cardiac rhythm management device can be programmed to determinethe LF/HF ratio by analyzing data received from its ventricular sensingchannels. The intervals between successive ventricular senses, referredto as RR intervals, can be measured and collected for a period of timeor a specified number of beats. In order to derive a signal representingheart rate variability during a sinus rhythm, ectopic ventricular beats(i.e., premature ventricular contractions or PVCs) can be detected bymonitoring whether a P wave precedes each R wave, with the RR intervalsbefore and after the PVC changed to an interpolated or otherwisefiltered value. The resulting series of RR interval values is thenstored as a discrete signal. The signal can be used directly as indexedby heartbeat such that each value of the signal represents an RRinterval for a particular heartbeat. Preferably, however, the signal isresampled at a specified sampling frequency in order to equalize thetime intervals between signal values and thus convert the signal into adiscrete time signal, where the sampling frequency is selected to meetthe Nyquist criterion with respect to the frequencies of interest. Inany case, the RR interval signal can then be analyzed to determine itsenergies in the high and low frequency bands as described above.Spectral analysis of an RR interval signal can be performed directly inthe frequency domain using discrete Fourier transform or autoregressiontechniques. Frequency domain analysis is computationally intensive,however, and may not be practical in an implantable device. Atime-domain technique for determining the high and low frequencycomponents of the signal is therefore preferably used. FIG. 1Billustrates the functional components of an exemplary system for doingthis that can be implemented as code executed by the controller and/ordedicated hardware components. The RR interval signal obtained asdescribed above is input to both a low band digital filter 201 and ahigh band digital filter 202. The low band filter 201 is a bandpassfilter with a passband corresponding to the LF band (e.g., 0.04 to 0.15Hz), while the high band filter 202 is a bandpass filter with a passbandcorresponding to the HF band (e.g., 0.15 to 0.40 Hz). The outputs offilters 201 and 202 are then input to power detectors 203 and 204,respectively, in order to derive signals proportional to the power ofthe RR interval signal in each of the LF and HF bands. Power detectionmay be performed, for example, by squaring the amplitude of the signaland integrating over a specified average time. The output of powerdetector 203 is thus a signal P1 that represents the power of the RRinterval signal in the LF band, and the output of power detector 204 isa signal P2 representing the power in the HF band. The signals P1 and P2are next input to a divider 205 that computes the quantity S1/S2 whichequals the LF/HF ratio. The LF/HF ratio is then input to a movingaverage filter 206 that computes an average value for the ratio over aspecified period (e.g., 5 minutes). An updated LF/HF ratio may becomputed in this manner on a beat-to-beat basis.

[0028] Another useful physiological variable that correlates withcardiac ischemia is the respiratory rate. Patients suffering a heartattack subjectively experience shortness of breath and attempt tocompensate by increasing their respiratory rate. The sensor normallyused for measuring minute ventilation can also be used to measurerespiratory rate, with drug delivery then being initiated only if themeasured respiratory rate is above a specified threshold value.

[0029] Another variable that may be useful in determining if drugtherapy for treating cardiac ischemia is warranted is the patient'sactivity level as measured by an accelerometer. Cardiac ischemia mayoccur while the patient is either active or at rest. Exertional angina,for example, occurs when a patient experiences cardiac pain from cardiacischemia due to an increased exertion level. If the angina is stable,meaning that the pain disappears when the patient's exertion levelreturns to a resting value, the situation is not ordinarily consideredemergent. It therefore may not be desirable for an implantable device toautomatically deliver a drug upon detection of cardiac ischemia in sucha situation. Accordingly, the device may be programmed to deliver drugtherapy only when cardiac ischemia is detected from the electrogram anda resting activity level is detected by the accelerometer as indicatedby the measured activity level being below a specified threshold value.

[0030] 4. Delivery of Cardiac Drugs

[0031] Once the controller 10 detects an ischemic change in anelectrogram warranting administration of a cardiac drug, a command isissued to the drug delivery interface 330. The drug delivery interfacethen actuates the drug delivery apparatus incorporated into the device,examples of which are illustrated in FIGS. 3 and 4A-B. In FIG. 3, acardiac rhythm management device is depicted which includes a metallichousing 100 and a header portion 110. Leads 120 used for sensing and/orpacing enter the header 110 and then pass into the interior of thehousing via feedthrough assemblies that maintain the hermetic sealing ofthe housing. A pump 340 and a drug reservoir 350 located within theheader 110 communicate with a catheter 360. The drug delivery interface330 within the housing communicates with the pump 340 by control wiresthat pass into the header through a feedthrough. Upon actuation by thedrug delivery interface 330, the pump 340 pumps a quantity of drug froma reservoir 350 into the lumen of a catheter 360. By locating the pumpand drug reservoir in the header, an external port 370 can be providedthrough which a quantity of drug can be injected in order to replenishthe reservoir.

[0032] The catheter 360 may be passed into patient intravenously alongwith the sensing/pacing leads so that the pumped quantity of drugegresses out the distal end of the catheter and into the patient'sbloodstream. The distal end of the catheter may also be disposed at acardiac location. In modifications to this embodiment, the catheter mayincorporate lead wires and electrodes for facilitating the drug deliverysuch as by iontophoresis, electroporation, electrorepulsion, orelectro-osmosis. The current to the electrodes in that case is thenactuated by the drug delivery interface in coordination with operationof the pump.

[0033]FIGS. 4A and 4B show an alternative embodiment where the distalend of the catheter 360 is attached to a patch electrode 400 foriontophoretic drug delivery. The patch electrode may, for example, bedisposed at a subcutaneous location on the patient's chest or abdomen.The patch electrode 400 has a drug reservoir 410 into which a quantityof drug is pumped by the pump 340 during a drug delivery operation. Aseparate lead 440 with a patch electrode 450 is also provided so that avoltage can be impressed across the patch electrodes 400 and 450 duringdrug delivery. The impressed voltage then causes migration of chargeddrug molecules from the reservoir and into the body tissues. In analternative embodiment, the patch electrodes 400 and 450 are mounted onthe device housing 100. External drug delivery means may also be used bythe device for drug delivery in response to ischemia. Examples ofexternal drug delivery apparatus are disclosed in U.S. Pat. No.6,361,522, assigned to the assignee of the present application andhereby incorporated by reference.

[0034] Finally, the device may be programmed to deliver drugs upondetection of conditions other than ischemia, which may be beneficial forcertain patients. For example, an anti-platelet drug or heparin may beadministered by the device when atrial fibrillation is detected.

[0035] Although the invention has been described in conjunction with theforegoing specific embodiment, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Such alternatives, variations, and modifications are intended to fallwithin the scope of the following appended claims.

What is claimed is:
 1. An implantable cardiac device, comprising: asensing channel for sensing cardiac activity; a pacing channel fordelivering pacing pulses; circuitry for recording an electrogram fromthe sensing channel of an evoked response to a pace and for detecting achange in the recorded electrogram indicative of cardiac ischemia bycomparing the recorded electrogram with a reference electrogram; a drugdelivery apparatus for delivering a quantity of a cardiac drug; and,circuitry for actuating the drug delivery apparatus upon detection ofcardiac ischemia.
 2. The device of claim 1 wherein the circuitry fordetecting a change in the recorded electrogram cross-correlates therecorded electrogram with the reference electrogram.
 3. The device ofclaim 1 the circuitry for detecting a change in the recorded electrogramlocates starting and end points of an ST segment using first and secondderivatives of the recorded electrogram.
 4. The device of claim 1wherein the circuitry for detecting a change in the recorded electrogramcompares the slope of an ST segment in the recorded electrogram with anST segment slope of the reference electrogram.
 5. The device of claim 1wherein the circuitry for detecting a change in the recorded electrogramcompares the amplitude of an ST segment with an ST segment amplitude ofthe reference electrogram.
 6. The device of claim 1 wherein thecircuitry for detecting a change in the recorded electrogram quantifiesthe degree of ischemia and further wherein the circuitry for causingdelivery of a cardiac drug does so only when the degree of ischemia isabove a programmable threshold value.
 7. The device of claim 1 whereinthe cardiac drug is a thrombolytic drug.
 8. The device of claim 1further comprising circuitry for analyzing the spectrum of intervalsbetween heartbeats detected by the sensing channel and computing anLF/HF ratio and wherein the circuitry for causing delivery of a cardiacdrug does so only when an ischemic condition is detected from therecorded electrogram and the LF/HF ratio exceeds a specified thresholdvalue.
 9. The device of claim 1 further comprising a minute ventilationsensor for measuring a patient's respiratory rate and wherein thecircuitry for causing delivery of a cardiac drug does so only when anischemic condition is detected from the recorded electrogram and therespiratory rate is above a specified threshold value
 10. The device ofclaim 1 further comprising an accelerometer for measuring a patient'sactivity level and wherein the circuitry for causing delivery of acardiac drug does so only when an ischemic condition is detected fromthe recorded electrogram and the measured activity level is below aspecified threshold value.
 11. A method for operating a cardiac deviceimplanted in a patient, comprising: sensing intrinsic cardiac activity;recording an electrogram from the sensed cardiac activity in order todetect a change indicative of cardiac isehemia; delivering a quantity ofa cardiac drug to the patient upon detection of cardiac ischemia; and,wherein a change in the recorded electrogram indicative of cardiacischemia is detected by comparing the recorded electrogram with areference electrogram and looking for an increased current of injury inthe recorded electrogram.
 12. The method of claim 11 further comprisinglooking for an increased current of injury by cross-correlating therecorded electrogram with the reference electrogram.
 13. The method ofclaim 11 further comprising looking for an increased current of injuryby locating starting and end points of an ST segment using first andsecond derivatives of the recorded electrogram.
 14. The method of claim11 further comprising looking for an increased current of injury bycomparing the slope of an ST segment in the recorded electrogram with anST segment slope of the reference electrogram.
 15. The method of claim11 further comprising looking for an increased current of injury bycomparing the amplitude of an ST segment with an ST segment amplitude ofthe reference electrogram.
 16. The method of claim 11 further comprisingquantifying the degree of ischemia and delivering a cardiac drug onlywhen the degree of ischemia is above a programmable threshold value. 17.The method of claim 11 wherein the cardiac drug is a thrombolytic drug.18. The method of claim 11 further comprising: analyzing the spectrum ofintervals between heartbeats and computing an LF/HF ratio; and,delivering a cardiac drug only when an ischemic condition is detectedfrom the recorded electrogram and the LF/HF ratio exceeds a specifiedthreshold value.
 19. The method of claim 11 further comprising:measuring the patient's respiratory rate; and, delivering a cardiac drugonly when an ischemic condition is detected from the recordedelectrogram and the respiratory rate is above a specified thresholdvalue
 20. The method of claim 11 further comprising: measuring thepatient's activity level; and, delivering a cardiac drug only when anischemic condition is detected from the recorded electrogram and themeasured activity level is below a specified threshold value.
 21. Animplantable cardiac device, comprising: means for sensing intrinsiccardiac activity; means for recording an electrogram from the sensedcardiac activity in order to detect a change indicative of cardiacischemia; means for delivering a quantity of a cardiac drug to thepatient upon detection of cardiac ischemia; and, means for detecting achange in the recorded electrogram indicative of cardiac ischemia bycomparing the recorded electrogram with a reference electrogramrepresentative of cardiac ischemia.
 22. The device of claim 21 furthercomprising means for cross-correlating the recorded electrogriam withthe reference electrogram.
 23. The device of claim 21 further comprisingmeans for locating starting and end points of an ST segment using firstand second derivatives of the recorded electrogram.
 24. The device ofclaim 21 further comprising means for comparing the slope of an STsegment in the recorded electrogram with an ST segment slope of thereference electrogram.
 25. The device of claim 21 further comprisingmeans for comparing the amplitude of an ST segment with an ST segmentamplitude of the reference electrogram.
 26. The device of claim 21further comprising means for quantifying the degree of ischemia anddelivering a cardiac drug only when the degree of ischemia is above aprogrammable threshold value.
 27. The device of claim 21 wherein thecardiac drug is a thrombolytic drug.
 28. The device of claim 21 furthercomprising: means for analyzing the spectrum of intervals betweenheartbeats and computing an LF/HF ratio; and, means for delivering acardiac drug only when an ischemic condition is detected from therecorded electrogram and the LF/HF ratio exceeds a specified thresholdvalue.
 29. The device of claim 21 further comprising: means formeasuring the patient's respiratory rate; and, means for delivering acardiac drug only when an ischemic condition is detected from therecorded electrogram and the respiratory rate is above a specifiedthreshold value
 30. The device of claim 21 further comprising: means formeasuring the patient's activity level; and, means for delivering acardiac drug only when an ischemic condition is detected from therecorded electrogram and the measured activity level is below aspecified threshold value.